Autonomic Pharm & Kinetics Flashcards
1
Q
On the log enzyme kinetics graph, y-intercept is equal to?
A
1/Vmax
2
Q
The lower the Km,
the _____ the affinity.
A
higher
3
Q
On the log kinetics graph:
Competitive inhibitors cross each other competitively.
T/F
A
T
They all cross on 1/Vmax
4
Q
On the log kinetics graph:
Noncompetitive inhibitors do not cross each other.
T/F
A
T
they have different Km’s
5
Q
Vd = ?
A
amt of drug in body /
plasma drug concentration
6
Q
t1/2 = ?
A
0.7 * Vd / clearanc
7
Q
A drug infused at a constant rate reaches about 94% of steady state after x half-lives?
A
x = 4
8
Q
Loading dose = ?
A
Cp * Vd/F
Cp = target plasma conc. F = bioavailability: =1 per IV
9
Q
Phase 1 metabolism involves?
yields?
A
reduction, oxidation, hydrolysis
cytochrome P450
yields slightly polar, still-active water-soluble metabolites
Geriatrics lost this first
10
Q
Phase 2 metabolism involves?
yields?
A
acetylation, glucuronidation, sulfation, conjugation
yields very polar, inactive metabolites
11
Q
Potency = ? Efficacy = ?
A
Potency = amt needed for a given effect
Efficacy = maximal effect
12
Q
Therapeutic index =
A
TD50 /
ED50
(median toxic dose /
median effective dose)
13
Q
Skeletal Muscle.
N or M?
neurotransmitter?
A
N
ACh
14
Q
PNS: Cardiac & Smooth Muscle, gland cells.
N or M?
neurotransmitter?
A
N——-M (2 neurons)
Ach Ach
15
Q
All sympathetic @ ganglion.
N or M?
neurotransmitter?
A
N
ACh
16
Q
Sympathetic 2nd neuron @ sweat glands:
N or M?
neurotransmitter?
A
M
ACh
17
Q
Sympathetic @ cardiac and smooth muscle, gland cells, nerve terminals
neurotransmitter?
A
NE @ alpha or beta
18
Q
Sympathetic at Renal vascular smooth muscle
receptor??
A
D1
19
Q
Sympathetic @ adrenal medulla
N or M?
neurotransmitter?
A
N, ACh
20
Q
G-protein-linked 2nd messengers:
a1 ->
G-prot class?
functions?
A
q
Inc’d vascular smooth muscle contraction
21
Q
G-protein-linked 2nd messengers:
a2
A
i Dec'd sympathetic outflow Dec'd insulin release Dec'd lipolysis Inc'd platelet aggregation
22
Q
G-protein-linked 2nd messengers:
B1
A
s Inc'd HR, Inc'd contactility Inc'd renin release Inc'd lipolysis
23
Q
G-protein-linked 2nd messengers:
B2
A
s vasodilation, bronchodilation Inc'd HR, contractility, lipolysis, insulin release, aqueous humor production Dec'd uterine tone (tocolysis) Ciliary muscle relaxation
24
Q
G-protein-linked 2nd messengers:
M1
A
q
CNS
25
G-protein-linked 2nd messengers:
| M2
i
| Dec'd HR & contractility of atria
26
G-protein-linked 2nd messengers:
| M3
q
Inc'd exocrine gland secretions, gut peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter muscle (miosis) & ciliary muscle contraction (accommodation)
27
G-protein-linked 2nd messengers:
| D1
s
| relaxes renal vascular smooth muscle
28
G-protein-linked 2nd messengers:
| D2
i
| modulates transmitter release, esp in brain
29
G-protein-linked 2nd messengers:
| H1
```
q
Inc'd nasal/bronchial mucus
bronchconstriction
pruritis
pain
```
30
G-protein-linked 2nd messengers:
| H2
s
| Inc'd gastic acid secretion
31
G-protein-linked 2nd messengers:
| V1
contracts vascular smooth muscle
32
G-protein-linked 2nd messengers:
| V2
Inc'd H20 permeability & reabsorption in the collective tubules
33
H1, a1, V1, M1, M3
G-prot class?
cell signals?
Gq --- Phoslipase C --- PIP2 --- DAG & IP3...
IP3 --- inc Ca (smooth muscle contraction
DAG --- PKC
34
B1, B2, D1, H2, V2
G-prot class?
cell signals?
Gs --- adenylcyclase --- (converts ATP into cAMP)...
cAMP --- PKA --- 2 actions:
1. inc'd Ca(2+) in heart
2. inhibits myosin light chain kinase (smooth muscle)
35
M2, a2, D2
Gi (inhibits) ---X adenylcyclase --- (converts ATP into cAMP)...
cAMP --- PKA --- 2 actions:
1. inc'd Ca(2+) in heart
2. inhibits myosin light chain kinase (smooth muscle)
36
Guanethidine
decreases NE release
37
Metyrosine
decreases DOPA formation from tyrosine
38
Reserpine
inhibits DA uptake into secretory vesicles; inhibiting its release @ nerve junction
39
Hemicholinium?
| Vesamicol?
H: inhibits presynaptic choline reuptake
V: inhibits ACh loading into secretory vesicles
40
Bethanechol
clin?
action?
cholinomimetic direct agonist
clin: postop & neurogenic ileus & urinary retention
action: activates Bowel & Bladder smooth muscle; resistant to AChE
41
Carbachol
clin?
action?
Cholinomimetic direct agonist
clin: glaucoma, pupillary contraction, & release of intraocular pressure
act: contracts ciliary muscle of eye (open angle), pupillar sphincter (narrow angle); resistant to AChE
42
Pilocarpine
cholinomimetic direct agonist
| potent stimulator of sweat, tears, saliva
43
Methacholine
cholinomimetic direct agonist
challenge test for dx of asthma
stimulates muscarinic receptors
44
Neostigmine
cholinomimetic indirect agonist
clin: postop & neurogenic ileus & urinary retention, myasthenia gravis, reversal of nueromuscular junction blockade(postop)
act: inc'd endogenous ACh; no CNS penetration
45
Pyridostigmine
cholinomimetic indirect agonist
myasthenia gravis, increases strength
act: inc'd endogenous ACh; no CNS penetrance
46
Edrophonium
cholinomimetic indirect agonist
dx of Myasthenia G (extremely short acting)
act: inc'd endogenous ACh;
47
Physostigmine
cholinomimetic indirect agonist
glaucoma (crosses BBB to CNS) and atropine OD
act: inc'd endogenous ACh;
48
Echothiophate
cholinomimetic indirect agonist
glaucoma
act: inc'd endogenous ACh;
49
Cholinesterase inhibitor poisoning symptoms:
antidote?
DUMBBELSS
```
Diarrhea
Urination
Miosis
Bronchospasm
Bradycardia
Excitation of skeletal muscle and CNS
Lacrimation
Sweating
Salivation (also abd cramps)
```
ANTIDOTE: atropine (muscarinic antagonist) plus pralidoxime (chemical antagonist used to regenerate active cholinsterase)
50
homatropine
tropicamide
atropine
Muscarinic antagonist (eye)
produces mydriasis & cycloplegia
51
Benztropine
Muscarinic antagonist (CNS)
parkinson's dz (2nd line)
52
Scopolamine
Muscarinic antagonist (CNS)
motion sickness
53
Ipratropium, Tiotropium
Muscarinic antagonist (respiratory)
Asthma, COPD
54
Oxybutynin, Glycopyrrolate
O: Muscarinic antagonist (genitourinary)
Reduces urgency in mild cystitis and reduces bladder spasms
G: Muscarinic antagonist (GI, respiratory)
Parenteral: pre-op to reduce airway secretions
Oral: drooling, peptic ulcer
55
Glaucoma
brimonide
mech?
tox?
mech: alpha agonist
_aqueous humor synth
SE: no pupillary or vision changes
56
Glaucoma
betaxolol, timolol, carteolol
mech?
tox?
mech: beta-blocker
_aqueous humor secretion
SE: no pupillary or vision changes
57
Glaucoma
Acetazolamide
mech?
tox?
mech: diuretic
_aqueous humor secretion via inhibition of carbonic anydrase
SE: no pupillary or vision changes
58
Glaucoma
pilocarpine, carbachol, physostigmine, echothiophate
mech?
tox?
mech: cholinomimetic
_outflow of aqueous humor; contracts ciliary muscle -->
opens trabecular meshwork
use pilocarpine in emergencies as it is very effetive at opening canal of Schlemm
SE: miosis, cyclospasm
59
Glaucoma
Latanoprost
mech?
tox?
mech: prostaglandin
_outflow of aqueous humor;
tox: darkens color of iris (browning)
60
ATROPINE
uses?
Muscarinic antagonist
```
EYE: _pupil dilation, cycloplegia
AIRWAY: _secretions
Stomach: _acid secretion
Gut: _motility
Bladder: _urgency in cystitis
```
```
BLOCKS SLUD:
Salivation
Lacrimation
Urination
Defecation
```
61
ATROPINE
tox?
TOX:
_body temp; rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation
can cause acute angle-closure glaucoma in elderly, urinary retention in men w/prostatic hypertrophy, and hyperthermia in infants
62
Hot as a...
```
Hot as a hare
Dry as a bone,
red as a beet,
blind as a bat
mad as a hatter
```
63
Hexamethonium
mech: nicotinic ACh receptor antagonist
clin: ganglionic blocker. Used in exp models to prevent vagal reflexz response to changes in BP--e.g. prevents reflex bradycardia caused by NE
64
Sympathomimetic selectivity
| Epi
__ __ __ __
low doses selective for __
uses: anaphylaxis, glaucoma(open angle), asthma, hypoTN
65
Sympathomimetic selectivity
| NE
__ __ > __
_SBP, DBP --> reflex bradycardia
clin:
hypoTN(but _renal perfusion)
66
Sympathomimetic selectivity
| Iso
__=__ > __ __
_SBP, DBP
_HR
clin: AV block (rare)
67
Sympathomimetic selectivity
| Dopa
D1=D2 > __ __ > __ __
clin:
shock(increases renal perfusion), HF
68
Sympathomimetic selectivity
| Dobu
__ __ __ __
69
Phenoxybenzamine (irrev)
| phentolamine (rev)
nonsel. _-blocker
clin: pheochromocytoma
tox: orthostatic HTN
reflex tachycardia
70
Prazosin, terazosin, doxazosin
__ selective
clin: HTN, BPH
tox: 1st dose orthoHTN, dizziness, headache
71
Mirtazapine
__ selective
clin: depression
tox: sedation, _serum chol, _appetite
72
olol's
clin & tox?
```
Beta-blockers
HTN: _CO, _renin secretion
Angina: _HR/contractility, resulting in _O2 use
MI: _mortality
SVT: _AV conduction velocity
CHF: slows progression of CHF
Glaucoma (timolol): _aq humor secretion
```
TOX: impotence, exacerabtion of asthma, CV adverse effects, CNS adverse effects
73
olol's
non selective & selective(A BEAM of b1 blockers)?
nonselective: propranolol, timolol, nadolol, pindolol (partial agonist), labetalol (partial agonist)
Beta1 selective: Acetbutolol (partial), betaxolol, Esmolol (short acting), Atenolol, Metroprolol
